The FDA has approved a second indication for plecanatide (Trulance, Synergy Pharmaceuticals Inc.): the once-daily treatment of irritable bowel syndrome with constipation (IBS-C) in adults. Plecanatide was already approved for the treatment of adults with chronic idiopathic constipation (CIC).
The 3-mg tablet is the only prescription medication for adults with CIC and now IBS-C that can be taken once daily, with or without food, at any time of the day.
“Approximately 1 in 20 Americans are living with IBS-C, many of whom are not satisfied with currently available treatment options,” said William D. Chey, MD, Professor of Medicine, Director of the GI Physiology Laboratory, and Co-Director of the Michigan Bowel Control Program at the University of Michigan.
With the exception of a single amino acid substitution for greater binding affinity, plecanatide is structurally identical to human uroguanylin and is the only treatment thought to replicate the pH-sensitive activity of uroguanylin.
The phase 3 IBS-C program for plecanatide included two randomized, 12-week, double-blind, placebo-controlled trials evaluating the efficacy and safety of the medication in adults with IBS-C. Across the two trials, more than 2,100 patients received a once-daily tablet of plecanatide (3 mg or 6 mg) or placebo. Both trials included a two-week, pre-treatment baseline period, a 12-week treatment period, and a two-week, post-treatment follow-up period. Patients met Rome III IBS-C criteria related to abdominal pain and stool changes.
The primary endpoint for both trials was the percentage of patients who were overall responders during the 12-week treatment period. An overall responder, as defined by the FDA, was a patient who fulfilled both at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) from baseline, in the same week, for at least 50% of the 12 treatment weeks.
In both phase 3 IBS-C trials, plecanatide met the primary endpoint as compared with placebo (Study 1: 30.2%; 17.8% in placebo; P < 0.001. Study 2: 21.5%; 14.2% in placebo; P = 0.009). Patients who received plecanatide experienced significantly reduced abdominal pain and improvements in stool frequency, stool consistency, and straining with bowel movements during the 12-week treatment period as compared to placebo.
In both studies, the most common adverse event was diarrhea (4.3%; 1.0% at placebo), with severe diarrhea reported in 1% of patients. Overall discontinuation rates were low among patients treated with plecanatide and placebo (2.5%; 0.4% at placebo) and the most common adverse reaction leading to discontinuation was diarrhea (1.2%; 0% in placebo).
Plecanatide is contraindicated in patients less than 6 years of age. In nonclinical studies in young juvenile mice, administration of a single oral dose of plecanatide caused deaths due to dehydration. Use of plecanatide should be avoided in patients 6 years to less than 18 years of age.
Source: Synergy Pharmaceuticals Inc.; January 25, 2018.